C hoeffel imaging of gastroenteropancreatic neuroendocrine tumors jfim hanoi 2015

Imaging of gastroenteropancrea0c neuroendocrine tumors

C.HOEFFEL CHU REIMS

Hanoi, nov 2015

Learning Objec0ves

•  Pathology •  Diagnosis and Local staging

– Pancreas – Small bowel

•  Distant staging •  Follow-‐up/Therapy monitoring •  Perspec0ves

General Considera0ons

•  Epithelial neoplasms with neuroendocrine differen0a0on expressing

– general markers such as chromogranin A and synaptophysin –  and neurone specific markers

•  Rare but incidence increasing over the past two decades •  Heterogeneous group of diseases with various clinical presenta0ons

– Inherited disorders (MEN, NF, VHL): small size and mul0ple-‐ 10 % – Vague or aspecific symptoms ( 2/3) – Func0onal symptoms – Unknown primary tumor in 15 % of cases

Lawrence B. Endoc Metab Clin N Am 2011

Treatment Op0ons

•  Surgery –  Primary –  Liver metastases (if no extrahepa0c disease)

•  Interven0onal Radiology and abla0ve therapies •  Medical treatment

–  Somatosta0n Analogues-‐ Interferon alpha –  Pep0de receptor targeted terapy/Novel targeted drugs –  Systemic chemotherapy (for higher grade)

•  Mul0disciplinary approach=> role of radiologist

•  Pathology –  High cellularity –  Hypervascular stroma but MVD variable from one tumor to another, even in same pa0ent

–  Liver metastases common, biopsied •  Before medical treatment •  Unknown Primary •  In pa0ents who have been resected from primary and for whom adapta0on of the treatment is necessary-‐changing or growing tumor

–  Histological grade assessment reliable en case of liver metastasis biopsy but less reliable with fine neddle cytology under EUS guidance

Pathology

Singh S. Eur J Surg Oncol. 2014

Pathology

WHO 2000 WHO 2010

1. Well differen0ated endocrine tumor Neuro endocrine tumor Grade 1

2. Well differen0ated endocrine carcinoma

Neuroendocrine tumor Grade 2

3. Poorly differen0ated endocrine carcinoma/ small cel neuroendocrine carcinoma (PDEC)

Neuroendocrine carcinoma Grade 3 (large or small cell type)

4. Mixed exocrine-‐endocrine carcinoma (MEEC) Tumor like lesions

Mixed adenoneuroendocrine carcinoma (MANEC) Hyperplas0c and preneoplas0c lesions

Grading Mitosis 10 HPF

KI67 index (%)

Grade 1 <2 ≤2

Grade 2 2-‐20 >2-‐20

Grade 3 >20 >20

Pathology –T stage Pancreas

•  Classifica0on UICC •  T0 No visible tumor •  T1 : T limited to p and < 2 cm •  T2 :T limited to p and > 2 cm •  T3: T extending beyond pancreas

but without extension to caeliac axis nor the superior mesenteric artery

•  T4 :T extending to caeliac axis or to superior mesenteric artery

•  Classifica0on ENETS •  T1: T limited to p and < 2 cm •  T2: T limited to p and from 2 to 4

cm •  T3: T invading duodenum or

biliary tract or T > 4 cm •  T4: T invading vessels, stomach,

spleen, colon, adrenal

Diagnosis and Local staging

•  Pancreas EUS/CT/MR •  Small bowel CT/MR

•  Mul0phasic: – Without IV –  Late arterial: 35 sec -‐40 sec –  Portal venous: 90 sec –  Late 3 min

•  Thin slices •  Variable sensi0vity-‐ up to 95 %

Manfredi Eur Radiol 2013

Pancrea0c NET-‐MDCT

–  Late arterial

enhancement 80 % –  dd: kidney mets,

intrapancrea0c spleen, pseudosolid serous cystadenoma

Cappelli et al. Eur Radiol 2015


–  Rare pancrea0c/Biliary duct dilata0on – Mismatch size of tumor and intact MPD

–  Venous encasement -‐ 1/3 of non func0onal tumors but no arterial involvement

Grade 3 Grade 2


•  Cys0c changes > 50 % up to 20 % of cases-‐ rim enhancement •  Kawamoto AJR 2013


Pancrea0c NET-‐ MRI

–  Sensi0vity up to 95 % –  If CT unconclusive/ Inherited

disorders –  Same features than CT –  Common features:

•  hyper T2++ 80 %, hyper or iso pancrea0c phase 76 % (dd adk), both 60 %

–  If enuclea0on •  Distance MPD-‐ Tumor •  Perop US and preop MR cholangiography

Caramella et al. European Radiol 2010 Manfredi Eur Radiol 2013 Brenner EJR 2012

T1 G1 Ki 1.5 % insulinoma-‐ enuclea0on under laparoscopy

Manfredi Eur Radiol 2013

Atypical appearance most frequently encountered in grade 3 tumors: ill-‐defined borders, hypovascular in art and venous phases, duct dilata0on

Pancrea0c NET-‐ MRI

DWI-‐MRI

•  Added value of DWI for Pancreas ? –  Increased detec0on on T2+ DWI –  ADC correlates well with Ki 67 index but contamina0on by perfusion characteris0cs

–  Differen0a0on between grade 1 vs 2 or 3 (40 p with pNETs) •  When any of the following 2 criteria was used, (a) tumor size smaller than 2.0 cm in diameter and (b) D value greater than 1.2×10(-‐3) mm(2)/s, the sensi0vity, specificity, and posi0ve predic0ve value for diagnosing grade 1 PNETs were 76.92%, 100%, and 100%, respec0vely

Brenner EJR 2012 Wang et al JMRI 2011 Hwang EJ Invest Radiol 2014

60 year-‐old man. Nega0ve SRS. Grade 2. Ki 4 %

B 500

Pancreas-‐ Endoscopic Ultrasound

•  Highly sensi0ve/specific –  head-‐ isthmic por0on (83-‐100 %) > distal body/tail.

•  Invasive, observer-‐dependent •  Indica0on ++

–  Clinical suspicion of pancrea0c NET with normal CT/MRI – Mul0ple endocrine neoplasia – When histology is necessary

Caramella et al. Eur Radiol 2010

•  40 % of tumors are located in last ileal cen0meters ++

•  Liver mets 20 % at diagnosis •  CT-‐enteroclysis = reference, if not seen at standard CT Se 95-‐100 %, Sp > 95 %

•  Focal, mul0ple in up to 20 % of cases

Woodbridge et al. Radiographics 2014 Kamaoui I AJR 2010

Small Bowel-‐ Local Staging

MDCT

•  Small submucosal mass or focal SB wall thickening

•  Mesenteric mass-‐ calcifica0on, spiculated •  Encasement of vessels -‐ arteries or veins •  SB Obstruc0on frequent

Specific assessment of the mesenteric complex

Stage II

Stage I

Stage III

Stage IV

Stage II

Stage I

Stage III

Stage IV

Lardière-‐Deguelte et al, Neuroendocrinology, in press

Iden0fy non or borderline resectable forms (IV and III)

TT= resec0on of primary lesion and mesenteric mass, evenif metastases Rela0onship between mesenteric involvement (lymph nodes or/and desmoplas0c mass) and superior mesenteric arteries and jejunal branches.

MR Enterography

•  Limited by lower spa0al resolu0on but high contrast resolu0on

•  In case of contraindica0on of CT •  Diffusion= no added value

Amzallag-‐Bellenger –Hoeffel C. Eur Radiol 2013 and Eur Radiol 2014

Distant Staging •  Metastases

–  Liver –  Peritoneal carcinomatosis for SB –  Lymph nodes-‐medias0num and neck –  Bone, Lung only if liver involved

KI 3 %

Distant Staging •  WELL DIFFERENTIATED

CT TAP Liver: MRI if doubt or if need to

resect Search for extrahepa0c mets when

liver mets are present SRS or Ga Dota Noc (par0cularly if

primary unknown or clinically suspected but invisible or if NET receptor radionuclide therapy)

•  Metabolic principle is the same but higher resolu0on and sensi0vity for detec0ng mets

•  POORLY DIFFERENTIATED (KI 67% >10%)

CT TAP TEP/CT Dedicated MR examina0on

depending on involved site

Metastases

•  Liver = major prognosis factor •  Assess tumor burden and

–  Type I = unilobar liver mets/ limited disease –  Type II= bilobar or complex liver metastases –  Type III= mul0ple or diffuse metastases

•  MR> CT> SRS •  “They are many more than you think”

Frilling. Lancet Oncol 2014 Elias Ann Surgery 2010 D’assignies Radiology 2013

MRI>CT Increased Sensi0vity and berer reproducibility Op0miza0on of protocol ++

Liver metastases

D’assignies Radiology 2013-‐ 41 p with 162 mets

Metastases

Metastases •  Best results= combina0on of sequences

D’assignies-Radiology 2013

DD: Angiome/HNF-‐rôle de l’échographie de contraste?

Metastases

Carcinomatosis

•  Small bowel •  Pancreas 10 % •  No specific studies •  Arterial phase •  Value of MRI

Follow-‐up •  Characteris0cs of GEP-‐NET

•  Slow evolu0on, numerous lesions, dissociated response •  Secre0on

•  RECIST •  Target choice •  Compare to nadir ≠ former CT •  Use dedicated sowware

What Imaging Technique?

New lesions

Janvier 2011

Juillet 2011 : CT _ MS IRM T1Gd + diffusion _ MP (2 nouvelles lésions)

•  Liver : MRI +++

15 mm

17 mm

T1Gd Diffusion

20/02/2015

03/10/2014

06/05/2015

Entre 20 et 40 secondes post IV, quatre acquisi0ons

Janvier 2015

Juin 2015 Everolimus + analogues somatosta0ne

Septembre 2015

Follow-‐up

•  Follow-‐up of the ac0ve tumoral volume?

January 2015 July 2015

RECIST : Σd 85 mm Σd 107 mm + 26% P m-‐RECIST : Σd 85 mm Σd 53 mm -‐ 38% RP

Follow-‐up

New lesions •  Whole body imaging : MRI, PET, Scin0graphy

SRS CT MRI T1Gd MRI DWI

PET Gallium 68

MRI Gallium PET

Schraml. Cancer Imaging. 2013 IRM vs 68Ga-‐DOTATOC, 51 pa0ents Per lesion analysis: TEP-‐Ga/CT = MRI but with differences PET (lung and lymph nodes), MRI (liver and bone)

Perspec0ves

EPI Ultrafast imaging with powerful gradients

Parrallel imaging Combine signal from

numerous elements of coil in phased array

Respiratory Ga0ng / trigger or echonavigator

Surface coil

Mobile table

Whole Body DWMR

•  Ax T2 FS •  Ax diffusion •  Coro T1 Spine

•  Gadolinium injec0on: Ax T1 EG arterial, portal on liver then pelvis

Positionnement des coupes

Axiales T2 FS-‐diff

Coronales T1

6 overlapping stacks (28 slices with no gap 7mm =19.6 cm) 2 overlapping stacks for spine

Protocol: DWI + standard MRI

Our Protocol

•  Currently under inves0ga0on

•  Ongoing study in France-‐ comparison to SRS

•  So far one study

•  Etchebehere. J Nuc Med. oct 2014 68Ga-‐

DOTATATE, 19 pa0ents

ü TEP/CT > IRM CE, mainly for bone lesions and

unknown primary

ü Absence of gado

Whole Body DWMR

Octréoscanner

scanner

Prognosis

•  Diffusion •  Perfusion characteris0cs?

– CT in 36 pNET – Correla0on between perfusion parameters (BF, MTT) and WHO grades

D’assignies G. Radiology 2009

European Radiology 2015. Capelli et al

19 pNETs 31 % No malignant NET

12 pNETs 20 % malignant

29 pNETs 48 % ½ carcinomas

Conclusion

•  CT = ref for diagnosis-‐ first line exam for ini0al staging but role of MRI and EUS for pancreas

•  Liver MRI for diagnosis of mets and follow-‐up –  Include diffusion

•  Op0mize and standardize protocols •  Follow-‐up: be aware of limits of RECIST •  Growing role of Diffusion-‐weighted whole-‐body MR imaging

C hoeffel imaging of gastroenteropancreatic neuroendocrine tumors jfim hanoi 2015

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